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Protein

Protein DJ-1

Gene

PARK7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease (PubMed:17015834, PubMed:20304780, PubMed:18711745, PubMed:12796482, PubMed:19229105, PubMed:25416785). It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway (PubMed:12612053, PubMed:15502874, PubMed:14749723, PubMed:17015834, PubMed:21097510, PubMed:18711745). Its involvement in protein repair could also explain other unrelated functions. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:16390825). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:19229105, PubMed:16632486). Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking (PubMed:18711745). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (PubMed:18626009). Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (PubMed:23792957). In macrophages, interacts with the NADPH oxidase subunit NCF1to direct NADPH oxidase-dependent ROS production, and protects against sepsis (By similarity). Has been described as a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) (PubMed:22523093, PubMed:25416785, PubMed:26995087, PubMed:28013050). However, another work ascribes the deglycation activity to a TRIS buffer artifact (PubMed:27903648).By similarity24 Publications

Catalytic activityi

An N(omega)-(1-hydroxy-2-oxopropyl)-[protein]-L-arginine + H2O = a [protein]-L-arginine + (R)-lactate.1 Publication
An N6-(1-hydroxy-2-oxopropyl)-[protein]-L-lysine + H2O = a [protein]-L-lysine + (R)-lactate.1 Publication
An S-(1-hydroxy-2-oxopropyl)-[protein]-L-cysteine + H2O = a [protein]-L-cysteine + (R)-lactate.1 Publication

Cofactori

Note: Deglycase activity does not require glutathione as a cofactor, however, glycated glutathione constitutes a PARK7 substrate.1 Publication

Kineticsi

kcat is 0.27 sec(-1) for the deglycation of glycated N-acetylarginine. kcat is 0.28 sec(-1) for the deglycation of glycated N-acetyllysine. kcat is 0.42 sec(-1) for the deglycation of glycated N-acetylcysteine.1 Publication
  1. KM=173.4 µM for casein1 Publication
  2. KM=0.44 mM for glycated N-acetylarginine (at pH 7.0 and 22 degrees Celsius)1 Publication
  3. KM=0.35 mM for glycated N-acetyllysine (at pH 7.0 and 22 degrees Celsius)1 Publication
  4. KM=0.32 mM for glycated N-acetylcysteine (at pH 7.0 and 22 degrees Celsius)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei106Nucleophile2 Publications1
    Active sitei1261 Publication1

    GO - Molecular functioni

    • androgen receptor binding Source: ParkinsonsUK-UCL
    • cadherin binding Source: BHF-UCL
    • copper ion binding Source: UniProtKB
    • cupric ion binding Source: ParkinsonsUK-UCL
    • cuprous ion binding Source: ParkinsonsUK-UCL
    • cytokine binding Source: ParkinsonsUK-UCL
    • enzyme binding Source: ParkinsonsUK-UCL
    • identical protein binding Source: IntAct
    • kinase binding Source: UniProtKB
    • L-dopa decarboxylase activator activity Source: ParkinsonsUK-UCL
    • mercury ion binding Source: UniProtKB
    • mRNA binding Source: UniProtKB
    • oxidoreductase activity, acting on peroxide as acceptor Source: ParkinsonsUK-UCL
    • peptidase activity Source: UniProtKB
    • peroxiredoxin activity Source: Ensembl
    • protein deglycase activity Source: ParkinsonsUK-UCL
    • protein homodimerization activity Source: UniProtKB
    • receptor binding Source: UniProtKB
    • repressing transcription factor binding Source: ParkinsonsUK-UCL
    • scaffold protein binding Source: ParkinsonsUK-UCL
    • small protein activating enzyme binding Source: ParkinsonsUK-UCL
    • superoxide dismutase copper chaperone activity Source: ParkinsonsUK-UCL
    • transcription coactivator activity Source: ParkinsonsUK-UCL
    • transcription factor binding Source: ParkinsonsUK-UCL
    • tyrosine 3-monooxygenase activator activity Source: ParkinsonsUK-UCL
    • ubiquitin-like protein conjugating enzyme binding Source: ParkinsonsUK-UCL
    • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL

    GO - Biological processi

    • activation of protein kinase B activity Source: ParkinsonsUK-UCL
    • adult locomotory behavior Source: Ensembl
    • autophagy Source: UniProtKB-KW
    • cellular response to glyoxal Source: ParkinsonsUK-UCL
    • cellular response to hydrogen peroxide Source: UniProtKB
    • cellular response to oxidative stress Source: ParkinsonsUK-UCL
    • detoxification of copper ion Source: UniProtKB
    • detoxification of mercury ion Source: UniProtKB
    • dopamine uptake involved in synaptic transmission Source: Ensembl
    • enzyme active site formation via L-cysteine sulfinic acid Source: Ensembl
    • glutathione deglycation Source: ParkinsonsUK-UCL
    • glycolate biosynthetic process Source: ParkinsonsUK-UCL
    • glyoxal metabolic process Source: ParkinsonsUK-UCL
    • hydrogen peroxide metabolic process Source: ParkinsonsUK-UCL
    • inflammatory response Source: UniProtKB-KW
    • lactate biosynthetic process Source: ParkinsonsUK-UCL
    • membrane depolarization Source: Ensembl
    • membrane hyperpolarization Source: Ensembl
    • methylglyoxal metabolic process Source: ParkinsonsUK-UCL
    • mitochondrion organization Source: UniProtKB
    • negative regulation of apoptotic process Source: ParkinsonsUK-UCL
    • negative regulation of cell death Source: UniProtKB
    • negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: ParkinsonsUK-UCL
    • negative regulation of death-inducing signaling complex assembly Source: ParkinsonsUK-UCL
    • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
    • negative regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
    • negative regulation of gene expression Source: ParkinsonsUK-UCL
    • negative regulation of hydrogen peroxide-induced cell death Source: ParkinsonsUK-UCL
    • negative regulation of hydrogen peroxide-induced neuron death Source: ParkinsonsUK-UCL
    • negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
    • negative regulation of neuron apoptotic process Source: BHF-UCL
    • negative regulation of neuron death Source: ParkinsonsUK-UCL
    • negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
    • negative regulation of oxidative stress-induced cell death Source: ParkinsonsUK-UCL
    • negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
    • negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
    • negative regulation of protein acetylation Source: ParkinsonsUK-UCL
    • negative regulation of protein binding Source: UniProtKB
    • negative regulation of protein export from nucleus Source: ParkinsonsUK-UCL
    • negative regulation of protein K48-linked deubiquitination Source: ParkinsonsUK-UCL
    • negative regulation of protein kinase activity Source: ParkinsonsUK-UCL
    • negative regulation of protein phosphorylation Source: ParkinsonsUK-UCL
    • negative regulation of protein sumoylation Source: ParkinsonsUK-UCL
    • negative regulation of protein ubiquitination Source: ParkinsonsUK-UCL
    • negative regulation of TRAIL-activated apoptotic signaling pathway Source: ParkinsonsUK-UCL
    • negative regulation of ubiquitin-protein transferase activity Source: ParkinsonsUK-UCL
    • negative regulation of ubiquitin-specific protease activity Source: ParkinsonsUK-UCL
    • peptidyl-arginine deglycation Source: ParkinsonsUK-UCL
    • peptidyl-cysteine deglycation Source: ParkinsonsUK-UCL
    • peptidyl-lysine deglycation Source: ParkinsonsUK-UCL
    • positive regulation of acute inflammatory response to antigenic stimulus Source: UniProtKB
    • positive regulation of androgen receptor activity Source: ParkinsonsUK-UCL
    • positive regulation of dopamine biosynthetic process Source: ParkinsonsUK-UCL
    • positive regulation of gene expression Source: ParkinsonsUK-UCL
    • positive regulation of interleukin-8 production Source: ParkinsonsUK-UCL
    • positive regulation of L-dopa biosynthetic process Source: ParkinsonsUK-UCL
    • positive regulation of L-dopa decarboxylase activity Source: ParkinsonsUK-UCL
    • positive regulation of mitochondrial electron transport, NADH to ubiquinone Source: ParkinsonsUK-UCL
    • positive regulation of mitophagy Source: ParkinsonsUK-UCL
    • positive regulation of NAD(P)H oxidase activity Source: UniProtKB
    • positive regulation of oxidative phosphorylation uncoupler activity Source: Ensembl
    • positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: Ensembl
    • positive regulation of peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
    • positive regulation of protein homodimerization activity Source: ParkinsonsUK-UCL
    • positive regulation of protein kinase B signaling Source: ParkinsonsUK-UCL
    • positive regulation of protein localization to nucleus Source: ParkinsonsUK-UCL
    • positive regulation of pyrroline-5-carboxylate reductase activity Source: ParkinsonsUK-UCL
    • positive regulation of reactive oxygen species biosynthetic process Source: Ensembl
    • positive regulation of sequence-specific DNA binding transcription factor activity Source: ParkinsonsUK-UCL
    • positive regulation of superoxide dismutase activity Source: ParkinsonsUK-UCL
    • positive regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
    • positive regulation of transcription regulatory region DNA binding Source: ParkinsonsUK-UCL
    • positive regulation of tyrosine 3-monooxygenase activity Source: ParkinsonsUK-UCL
    • protein deglycation, glyoxal removal Source: ParkinsonsUK-UCL
    • protein deglycation, methylglyoxal removal Source: ParkinsonsUK-UCL
    • protein deglycosylation Source: UniProtKB
    • protein stabilization Source: ParkinsonsUK-UCL
    • Ras protein signal transduction Source: ParkinsonsUK-UCL
    • regulation of androgen receptor signaling pathway Source: UniProtKB
    • regulation of inflammatory response Source: UniProtKB
    • regulation of mitochondrial membrane potential Source: ParkinsonsUK-UCL
    • regulation of neuron apoptotic process Source: UniProtKB
    • regulation of supramolecular fiber organization Source: ParkinsonsUK-UCL
    • single fertilization Source: UniProtKB-KW

    Keywordsi

    Molecular functionChaperone, Hydrolase, Protease, RNA-binding
    Biological processAutophagy, Fertilization, Inflammatory response, Stress response
    LigandCopper

    Enzyme and pathway databases

    SABIO-RKiQ99497.
    SignaLinkiQ99497.
    SIGNORiQ99497.

    Protein family/group databases

    MEROPSiC56.002.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein DJ-1Curated
    Short name:
    DJ-1
    Alternative name(s):
    Oncogene DJ1Curated
    Parkinson disease protein 7Curated
    Parkinsonism-associated deglycaseImported
    Protein deglycase DJ-11 Publication (EC:3.1.2.-1 Publication, EC:3.5.1.1241 Publication)
    Gene namesi
    Name:PARK7Imported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:16369. PARK7.

    Subcellular locationi

    GO - Cellular componenti

    • axon Source: ParkinsonsUK-UCL
    • cell body Source: Ensembl
    • cell-cell adherens junction Source: BHF-UCL
    • chromatin Source: ParkinsonsUK-UCL
    • cytoplasm Source: UniProtKB
    • cytosol Source: UniProtKB
    • endoplasmic reticulum Source: Ensembl
    • extracellular exosome Source: UniProtKB
    • membrane raft Source: UniProtKB-SubCell
    • mitochondrial intermembrane space Source: Ensembl
    • mitochondrial matrix Source: Ensembl
    • mitochondrion Source: UniProtKB
    • nucleus Source: UniProtKB
    • perinuclear region of cytoplasm Source: BHF-UCL
    • plasma membrane Source: UniProtKB-SubCell
    • PML body Source: ParkinsonsUK-UCL
    • presynapse Source: GOC

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Mitochondrion, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Parkinson disease 7 (PARK7)12 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease).
    See also OMIM:606324
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02049226M → I in PARK7; does not affect protein stability and degradation; does not interfere with homodimerization. 2 PublicationsCorresponds to variant dbSNP:rs74315351Ensembl.1
    Natural variantiVAR_02049364E → D in PARK7; no apparent effect on protein stability; impaired mitochondrial morphology. 3 PublicationsCorresponds to variant dbSNP:rs74315353Ensembl.1
    Natural variantiVAR_020495104A → T in PARK7; Loss of protection against metal cytotoxicity. 2 PublicationsCorresponds to variant dbSNP:rs774005786Ensembl.1
    Natural variantiVAR_020496149D → A in PARK7; Loss of protection against metal cytotoxicity. 2 PublicationsCorresponds to variant dbSNP:rs74315352Ensembl.1
    Natural variantiVAR_020498166L → P in PARK7; strongly decreases enzymatic activity; reduces protein stability and leads to increased degradation; ubiquitinated by PRKN leading to its recognition by HDAC6 and targeting to aggresome where is degraded; interferes with homodimerization; abolishes interaction with PIAS2; reduced localization in lipid rafts. 8 PublicationsCorresponds to variant dbSNP:rs28938172Ensembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi18E → A: Strongly decreases enzymatic activity. 1 Publication1
    Mutagenesisi18E → D: Strongly decreases enzymatic activity. 1 Publication1
    Mutagenesisi18E → N: Strongly decreases enzymatic activity. 1 Publication1
    Mutagenesisi18E → Q: Strongly decreases enzymatic activity. 1 Publication1
    Mutagenesisi46C → A: Reduced localization in lipid rafts; when associated with A-106. 4 Publications1
    Mutagenesisi46C → A: Reduces protein stability. No effect on oxidation. 4 Publications1
    Mutagenesisi46C → S: No effect on mitochondrial translocation neither on deglycase activity. 5 Publications1
    Mutagenesisi51V → A: Disrupts dimer formation and strongly reduces ability to eliminate hydrogen peroxide. 1 Publication1
    Mutagenesisi53C → A: Strongly reduces chaperone activity and ability to eliminate hydrogen peroxide. 4 Publications1
    Mutagenesisi53C → S: No effect on mitochondrial translocation neither on deglycase activity. 5 Publications1
    Mutagenesisi106C → A: Abolishes enzymatic activity. Abolishes oxidation, association with mitochondria and protease activity. No effect on chaperone activity. Reduced binding to OTUD7B. 8 Publications1
    Mutagenesisi106C → A: Reduced localization in lipid rafts; when associated with A-46. 7 Publications1
    Mutagenesisi106C → D: Abolishes oxidation and association with mitochondria. No effect on chaperone activity. 7 Publications1
    Mutagenesisi106C → S: Loss of deglycase activity. No effect on mitochondrial translocation. Reduced protease activity. No effect on protection against metal cytotoxicity. 8 Publications1
    Mutagenesisi126H → A: Strongly decreases enzymatic activity. 2 Publications1
    Mutagenesisi130K → R: Partially compensates for loss of stability; when associated with P-166. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism, Tumor suppressor

    Organism-specific databases

    DisGeNETi11315.
    GeneReviewsiPARK7.
    MalaCardsiPARK7.
    MIMi168600. phenotype.
    606324. phenotype.
    OpenTargetsiENSG00000116288.
    Orphaneti90020. Amyotrophic lateral sclerosis-parkinsonism-dementia complex.
    2828. Young adult-onset Parkinsonism.
    PharmGKBiPA32946.

    Polymorphism and mutation databases

    BioMutaiPARK7.
    DMDMi56404943.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    PropeptideiPRO_0000405558? – 189Removed in mature form
    Initiator methionineiRemovedCombined sources
    ChainiPRO_00001578492 – ?Protein DJ-1

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylalanineCombined sources1
    Lipidationi46S-palmitoyl cysteine1 Publication1
    Lipidationi53S-palmitoyl cysteine1 Publication1
    Modified residuei67PhosphotyrosineCombined sources1
    Modified residuei106Cysteine sulfinic acid (-SO2H); alternate1 Publication1
    Lipidationi106S-palmitoyl cysteine; alternate1 Publication1
    Cross-linki130Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
    Modified residuei148N6-acetyllysineBy similarity1
    Modified residuei182N6-succinyllysineBy similarity1

    Post-translational modificationi

    Sumoylated on Lys-130 by PIAS2 or PIAS4; which is enhanced after ultraviolet irradiation and essential for cell-growth promoting activity and transforming activity.1 Publication
    Cys-106 is easily oxidized to sulfinic acid.2 Publications
    Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.1 Publication

    Keywords - PTMi

    Acetylation, Isopeptide bond, Lipoprotein, Oxidation, Palmitate, Phosphoprotein, Ubl conjugation, Zymogen

    Proteomic databases

    EPDiQ99497.
    PaxDbiQ99497.
    PeptideAtlasiQ99497.
    PRIDEiQ99497.
    TopDownProteomicsiQ99497.

    2D gel databases

    OGPiQ99497.
    REPRODUCTION-2DPAGEiIPI00298547.
    UCD-2DPAGEiQ99497.

    PTM databases

    iPTMnetiQ99497.
    PhosphoSitePlusiQ99497.
    SwissPalmiQ99497.

    Miscellaneous databases

    PMAP-CutDBiQ99497.

    Expressioni

    Tissue specificityi

    Highly expressed in pancreas, kidney, skeletal muscle, liver, testis and heart. Detected at slightly lower levels in placenta and brain (at protein level). Detected in astrocytes, Sertoli cells, spermatogonia, spermatids and spermatozoa.4 Publications

    Inductioni

    By hydrogen peroxide and UV irradiation.2 Publications

    Gene expression databases

    BgeeiENSG00000116288.
    CleanExiHS_PARK7.
    ExpressionAtlasiQ99497. baseline and differential.
    GenevisibleiQ99497. HS.

    Organism-specific databases

    HPAiCAB005870.
    HPA004190.

    Interactioni

    Subunit structurei

    Homodimer (PubMed:12851414, PubMed:12796482, PubMed:12855764). Binds EFCAB6/DJBP and PIAS2 (PubMed:11477070, PubMed:12851414, PubMed:12612053). Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR (PubMed:12612053). Interacts (via N-terminus) with OTUD7B (PubMed:21097510). Interacts with BBS1, HIPK1, CLCF1 and MTERF (PubMed:16390825, PubMed:21097510). Forms a complex with PINK1 and PRKN (PubMed:19229105). Interacts (via C-terminus) with NCF1; the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation (By similarity).By similarity7 Publications

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    • androgen receptor binding Source: ParkinsonsUK-UCL
    • cadherin binding Source: BHF-UCL
    • cytokine binding Source: ParkinsonsUK-UCL
    • enzyme binding Source: ParkinsonsUK-UCL
    • identical protein binding Source: IntAct
    • kinase binding Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB
    • receptor binding Source: UniProtKB
    • repressing transcription factor binding Source: ParkinsonsUK-UCL
    • scaffold protein binding Source: ParkinsonsUK-UCL
    • small protein activating enzyme binding Source: ParkinsonsUK-UCL
    • transcription factor binding Source: ParkinsonsUK-UCL
    • ubiquitin-like protein conjugating enzyme binding Source: ParkinsonsUK-UCL
    • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL

    Protein-protein interaction databases

    BioGridi116446. 88 interactors.
    DIPiDIP-35515N.
    IntActiQ99497. 45 interactors.
    MINTiMINT-5003468.
    STRINGi9606.ENSP00000340278.

    Structurei

    Secondary structure

    1189
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi5 – 10Combined sources6
    Helixi16 – 28Combined sources13
    Beta strandi32 – 37Combined sources6
    Turni38 – 41Combined sources4
    Beta strandi47 – 49Combined sources3
    Beta strandi51 – 53Combined sources3
    Beta strandi55 – 57Combined sources3
    Helixi58 – 62Combined sources5
    Beta strandi68 – 72Combined sources5
    Helixi76 – 84Combined sources9
    Helixi86 – 97Combined sources12
    Beta strandi101 – 105Combined sources5
    Turni106 – 108Combined sources3
    Helixi109 – 114Combined sources6
    Helixi127 – 129Combined sources3
    Helixi130 – 133Combined sources4
    Turni134 – 136Combined sources3
    Beta strandi139 – 141Combined sources3
    Beta strandi145 – 149Combined sources5
    Beta strandi152 – 155Combined sources4
    Helixi158 – 160Combined sources3
    Helixi161 – 173Combined sources13
    Helixi175 – 182Combined sources8
    Helixi183 – 185Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1J42X-ray2.50A1-189[»]
    1P5FX-ray1.10A1-189[»]
    1PDVX-ray1.80A1-189[»]
    1PDWX-ray2.20A/B/C/D/E/F/G/H1-189[»]
    1PE0X-ray1.70A/B1-189[»]
    1Q2UX-ray1.60A1-189[»]
    1SOAX-ray1.20A1-189[»]
    1UCFX-ray1.95A/B1-189[»]
    2OR3X-ray1.20A/B1-189[»]
    2R1TX-ray1.70A/B2-188[»]
    2R1UX-ray1.50A/B2-188[»]
    2R1VX-ray1.70A/B2-188[»]
    2RK3X-ray1.05A1-189[»]
    2RK4X-ray1.15A1-189[»]
    2RK6X-ray1.15A1-189[»]
    3B36X-ray1.50A1-189[»]
    3B38X-ray1.85A1-189[»]
    3B3AX-ray1.50A1-189[»]
    3BWEX-ray2.40A/B/C/D/E/F/G1-189[»]
    3CY6X-ray1.35A1-189[»]
    3CYFX-ray1.60A1-189[»]
    3CZ9X-ray1.15A1-189[»]
    3CZAX-ray1.20A1-189[»]
    3EZGX-ray1.15A1-189[»]
    3F71X-ray1.20A1-189[»]
    3SF8X-ray1.56A/B1-189[»]
    4BTEX-ray1.38A1-189[»]
    4MNTX-ray1.58A1-189[»]
    4MTCX-ray1.47A1-189[»]
    4N0MX-ray1.95A1-189[»]
    4N12X-ray1.48A1-189[»]
    4OGFX-ray1.60A2-188[»]
    4OQ4X-ray1.49A1-189[»]
    4P2GX-ray1.35A1-189[»]
    4P34X-ray1.55A1-189[»]
    4P35X-ray1.75A1-189[»]
    4P36X-ray1.18A1-189[»]
    4RKWX-ray1.50A1-189[»]
    4RKYX-ray1.50A1-189[»]
    4S0ZX-ray1.45A1-189[»]
    4ZGGX-ray1.23A1-189[»]
    5IP5X-ray1.66A1-189[»]
    5SY6X-ray1.15A1-189[»]
    5SY9X-ray1.10A1-189[»]
    5SYAX-ray1.10A1-189[»]
    ProteinModelPortaliQ99497.
    SMRiQ99497.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ99497.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase C56 family.Curated

    Phylogenomic databases

    eggNOGiKOG2764. Eukaryota.
    COG0693. LUCA.
    GeneTreeiENSGT00390000001231.
    HOGENOMiHOG000063194.
    HOVERGENiHBG053511.
    InParanoidiQ99497.
    KOiK05687.
    OMAiTCYPGFE.
    OrthoDBiEOG091G12NS.
    PhylomeDBiQ99497.
    TreeFamiTF300119.

    Family and domain databases

    Gene3Di3.40.50.880. 1 hit.
    InterProiView protein in InterPro
    IPR029062. Class_I_gatase-like.
    IPR002818. DJ-1/PfpI.
    IPR006287. DJ1.
    PfamiView protein in Pfam
    PF01965. DJ-1_PfpI. 1 hit.
    SUPFAMiSSF52317. SSF52317. 1 hit.
    TIGRFAMsiTIGR01383. not_thiJ. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q99497-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MASKRALVIL AKGAEEMETV IPVDVMRRAG IKVTVAGLAG KDPVQCSRDV
    60 70 80 90 100
    VICPDASLED AKKEGPYDVV VLPGGNLGAQ NLSESAAVKE ILKEQENRKG
    110 120 130 140 150
    LIAAICAGPT ALLAHEIGFG SKVTTHPLAK DKMMNGGHYT YSENRVEKDG
    160 170 180
    LILTSRGPGT SFEFALAIVE ALNGKEVAAQ VKAPLVLKD
    Length:189
    Mass (Da):19,891
    Last modified:July 5, 2004 - v2
    Checksum:i4B21661B3A76BC67
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti119F → C in BAB71782 (Ref. 3) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02049226M → I in PARK7; does not affect protein stability and degradation; does not interfere with homodimerization. 2 PublicationsCorresponds to variant dbSNP:rs74315351Ensembl.1
    Natural variantiVAR_07258939A → S Probable disease-associated mutation found in early-onset Parkinson disease with digenic inheritance; the patient also carries PINK1 mutation L-399. 1 PublicationCorresponds to variant dbSNP:rs137853051Ensembl.1
    Natural variantiVAR_02049364E → D in PARK7; no apparent effect on protein stability; impaired mitochondrial morphology. 3 PublicationsCorresponds to variant dbSNP:rs74315353Ensembl.1
    Natural variantiVAR_02049498R → Q4 PublicationsCorresponds to variant dbSNP:rs71653619Ensembl.1
    Natural variantiVAR_020495104A → T in PARK7; Loss of protection against metal cytotoxicity. 2 PublicationsCorresponds to variant dbSNP:rs774005786Ensembl.1
    Natural variantiVAR_020496149D → A in PARK7; Loss of protection against metal cytotoxicity. 2 PublicationsCorresponds to variant dbSNP:rs74315352Ensembl.1
    Natural variantiVAR_020497150G → S1 PublicationCorresponds to variant dbSNP:rs368420490Ensembl.1
    Natural variantiVAR_034801163E → K1 PublicationCorresponds to variant dbSNP:rs74315354Ensembl.1
    Natural variantiVAR_020498166L → P in PARK7; strongly decreases enzymatic activity; reduces protein stability and leads to increased degradation; ubiquitinated by PRKN leading to its recognition by HDAC6 and targeting to aggresome where is degraded; interferes with homodimerization; abolishes interaction with PIAS2; reduced localization in lipid rafts. 8 PublicationsCorresponds to variant dbSNP:rs28938172Ensembl.1
    Natural variantiVAR_020499171A → S1 PublicationCorresponds to variant dbSNP:rs777026628Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D61380 mRNA. Translation: BAA09603.2.
    AF021819 mRNA. Translation: AAC12806.1.
    AB073864 mRNA. Translation: BAB71782.1.
    AK312000 mRNA. Translation: BAG34938.1.
    AL034417 Genomic DNA. No translation available.
    CH471130 Genomic DNA. Translation: EAW71591.1.
    BC008188 mRNA. Translation: AAH08188.1.
    AB045294 Genomic DNA. No translation available.
    AY648999 Genomic DNA. Translation: AAT68961.1.
    CCDSiCCDS93.1.
    PIRiJC5394.
    RefSeqiNP_001116849.1. NM_001123377.1.
    NP_009193.2. NM_007262.4.
    XP_005263481.1. XM_005263424.3.
    UniGeneiHs.419640.

    Genome annotation databases

    EnsembliENST00000338639; ENSP00000340278; ENSG00000116288.
    ENST00000377488; ENSP00000366708; ENSG00000116288.
    ENST00000377491; ENSP00000366711; ENSG00000116288.
    ENST00000493373; ENSP00000465404; ENSG00000116288.
    ENST00000493678; ENSP00000418770; ENSG00000116288.
    GeneIDi11315.
    KEGGihsa:11315.

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiPARK7_HUMAN
    AccessioniPrimary (citable) accession number: Q99497
    Secondary accession number(s): B2R4Z1
    , O14805, Q6DR95, Q7LFU2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
    Last sequence update: July 5, 2004
    Last modified: August 30, 2017
    This is version 180 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Caution

    Glyoxalase activity was previously reported (PubMed:22523093). It may however reflect its deglycase activity (PubMed:25416785).2 Publications
    The deglycase function of this protein is not unanimous among researchers and is the subject of some controversy (PubMed:25416785, PubMed:27903648, PubMed:28013050). The deglycation activity has been ascribed to a TRIS buffer artifact by a publication, however another work disputes these results (PubMed:27903648, PubMed:28013050).3 Publications

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families